Recent research suggests that patients who take ACE inhibitors may face a higher risk of five-year mortality and major adverse cardiovascular events (MACE) compared to those taking ARBs. This study, however, has sparked debate among experts regarding its findings and methodology.
The cohort study in question analyzed data from 72,000 patients in the UK and 255,000 in China, all newly prescribed either ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers). The findings indicated that at the five-year follow-up, new users of ARBs had a lower risk of all-cause mortality compared to those on ACE inhibitors.
Key Findings and Data
In the UK cohort, there were 696 all-cause deaths (3.45%) among ACE inhibitor users, compared to 630 deaths (3.04%) among ARB users. Similarly, in the Chinese cohort, the five-year cumulative incidence of all-cause mortality was 16% for ACE inhibitor initiators and 15% for ARB initiators.
“The reduced mortality risk associated with ARBs use may partly be explained by a lower incidence of MACE,” the researchers stated in their publication in Hypertension.
The study underscores the importance of carefully selecting renal angiotensin-aldosterone system inhibitors, considering both effectiveness and safety.
Expert Opinions and Criticisms
Despite the study’s large sample size, Professor Thomas Marwick, a cardiologist and professorial research fellow at the Baker Heart and Diabetes Institute, has raised concerns about the research. He points out the presence of unmeasured confounders and significant differences in baseline characteristics between the UK and Chinese cohorts.
For example, the mean BMI was 29 in the UK cohort and 21 in the Chinese cohort, while LDL cholesterol levels were 1.6 in the UK group compared to 2.7 in the Chinese participants. Additionally, heart failure treatment rates varied significantly, with 2% of UK participants and 18% of the Chinese cohort receiving treatment.
“The numbers obviously are huge, which is the attraction, but the disadvantage is that the granularity of the data is not enough to make what is a really important distinction. I just don’t think the data is up to it,” Professor Marwick told The Medical Republic.
Comparative Efficacy and Side Effects
Professor Marwick emphasized that ACE inhibitors and ARBs have “comparable efficacy” in treating hypertension. He noted that while both drug classes have different side effects, ARBs are generally better tolerated and preferred in general practice.
“Each of them have got somewhat different side effects. Probably the ARBs are better tolerated, and the ARBs, I would say, are probably generally preferred in general practice,” he explained.
However, Marwick cautioned that the study’s findings are based on a comparison of drug use in databases with significantly different patient risk profiles. He argued that statistical modeling alone might not adequately account for these differences.
“What they’ve given us here is a comparison of the use of the agents, not necessarily for hypertension, in databases where the associated risks of the patients are actually quite different, so you’re asking the statistical modelling to try and overcome some pretty significant differences in the profiles of the patients. And I think it’s too much to ask the stats to do,” he said.
Implications and Future Research
While the study’s results may be “hypothesis generating,” Professor Marwick believes they are not conclusive. He highlighted the limitations of observational data sets, which can produce large numbers but may not accurately reflect practical questions.
“It’s a reminder of the limitation of observational data sets, that you can crank up big numbers but you’ve got to be really careful about whether that corresponds to what the question is in practice,” he concluded.
This ongoing debate underscores the need for further research to better understand the comparative safety and efficacy of ACE inhibitors versus ARBs, particularly in diverse populations. As the medical community continues to explore these questions, patients and healthcare providers must weigh the available evidence carefully when making treatment decisions.
